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P63 Pregnancy management in women with history of obsteric complications: did thrombophilia change our strategy?
3rd Women’s Health Issues in Thrombosis and Haemostasis P60 Factor XIII Val34Leu polymorphism in patients surviving or not surviving ischemic stroke A.H. Shemirani1 , B. Antalffy2 , E. Pongr´ acz3 , L. Muszbek1 . 1 Clinical Research Center, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary, 2 Department of Pathology, Di´ osgy˝ ori Vasgy´ ari Hospital, Miskolc, Hungary, 3 Department of Neurology, State Health Center, Budapest, Hungary Objectives: The results published on the association of FXIII-A Val34Leu polymorphism with the risk of ischemic stroke have been inconclusive. In these studies stroke survivors and nonsurvivors were not analyzed separately. Here, we investigated the effect of the polymorphism on the occurrence and the lethal outcome of ischemic stroke. Design and Methods: FXIII-A Val34Leu genotype of 508 patients who survived ischemic stroke (median age: 50) and 508 age- and sex-matched controls was determined using melting point analysis and FRET detection. DNA samples for genotyping were also isolated from tissue sections of 461 patients who died of ischemic stroke (mean age: 74) and the results were compared to a sex-matched population control group. Results: FXIII-A Val34Leu genotype had no effect on the risk of non-lethal stroke. Similarly, heterozygous Val34Leu polymorphism and Leu34 carriership did represent a significant risk of stroke with lethal outcome. However, homozygosity to Val34Leu polymorphism conferred a significant risk of lethal stroke to females (OR: 2.914, CI: 1.324 6.415); while in males the increase of the risk was not statistically significant (OR: 1.605, CI: 0.696 3.704). Conclusion: The homozygous form of FXIII-A Val34Leu polymorphism significantly increased the risk of stroke with lethal outcome in females. P61 Abnormal uterine bleeding and defects in system hemostasis R. Saidova, A. Makatsaria. Department of Obstetrics and Gynecology, Moscow Sechenov Medical Academy, Moscow, Russia Background: It is known that abnormal uterine bleeding (AUB) is the manifestation of various cases like leiomyoma (43.9%), adenomyosis (42 50%), bleeding in perimenopause due to the hyperplasia of endometrium (9.5 30.6%), endomethritisthe (41.9 99.2%). The uterine bleeding may also be seen in patients with hemorrhagic syndrome such as Von Willebrand Disease (50 70%), inherited forms of hemophilia (55 75%), thrombocytopatia and thrombocytopenia (70 80%). Material and Methods: Since 1985 up to 2008 we have observed more than 1,000 AUB patients of 12 to 55 years old. Disorders were detected via ultrasound, hormonal status and histopathological investigation. Functional tests for hemostasis were also performed. The disorders were divided into anovulatory and ovulatory states and hypo- and hyperoestrogen states. Results: Our examination showed that the most of patients of early reproductive age suffered from hypoestrogenic disorders, with 68.8% of cases being hypoestrogenic anovulation. In late reproductive age and in the perimenopausal period hyperoestrogenic types of disfunction were observed. 57.9% of women of late reproductive age and 87.5 % of perimenopausal period had hyperoestrogenic anovulation. Middle reproductive age proved to be the most stable period of reproductive system, with 71% of cases showing luteal phase disfunction. Von Willebrand Disease and syndrome were diagnosed in 25.3% and 12.8% of cases respectively, thrombocytopenia 7.3%, thrombocytopatia 48.7%, defects of the plasma coagulation factors 5.9%.
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Conclusion: In most cases of abnormalities of the reproductive system the hemorrhagic changes in hemostasis combined form of AUB was observed. P62 Thrombophilia and prosthetic valve thrombosis in pregnancy S.V. Akinshina, V.O. Bitsadze, V.B. Nemirovskiy, N.T. Meskhi, A.D. Makatsaria. Department of Obstetrics and Gynecology, I.M. Sechenov Moscow Medical Academy, Russia Aim: To determine genetic thrombophilia and antiphospholipid antibodies (APA) in pregnant women with prosthetic valve thrombosis. Material and Methods: We have examined 8 pregnant women (25.7 ± 3.5 years) with mechanical valve thrombosis (mitral valve n = 6, aortic valve n = 1, tricuspid valve n = 1). Analysis of thrombophilia and APA was performed in all patients. Results: History of obstetric complications (recurrent fetal loss, intrauterine growth restriction, preeclampsia, antenatal death) was observed in 3 women. Thromboembolic complications were observed in 4 women (stroke n = 2, renal and spleen thrombosis n = 1, iliofemoral thrombosis after cesarean section n = 1). Before the admission to our hospital (in 8 28 weeks of gestation) 5 patients received warfarin without regular LMWH in low doses. 1 patient did monitoring, 3 patients not receive any anticoagulants in pregnancy during 1 month. Fetal mortality was 50% (n = 4). One patient died due to pulmonary embolism 48 hours after the simultaneous cesarean section and valve replacement. Multigenic thrombophilia (8805; 4 mutations concomitantly) and APA were detected in 100%. MTHFR C677T, PAI-1 675 4G/5G, t-PA I/D, F Hageman 46C/T, fibrinogen 455G/A, FV Leiden, prothrombin G20210A were detected in 6, 6, 2, 2, 4, 2 and 2 cases respectively. Lupus anticoagulant, anti-beta-glycoprotein I, anticardiolipins, antiannexin V antibodies were detected in 3, 6, 2 and 3 patients respectively. Conclusion: Prosthetic valve thrombosis in pregnancy may be associated with hypercoagulation state and inadequate anticoagulation in women with multigenic thrombophilia and APA-circulation. P63 Pregnancy management in women with history of obsteric complications: did thrombophilia change our strategy? A.D. Makatsaria, V.O. Bitsadze, S.M. Baimuradova, S.V. Akinshina. Department of Obstetrics and Gynecology, I.M. Sechenov Moscow Medical academy, Russia Aims: To determine genetic thrombophilia and to evaluate maternal and fetal outcomes in women with history of pregnancy complications receiving the preconception treatment. Material and methods: During the last 7 years we examined a total of 800 patients with history of pregnancy complications: 400 patients with fetal loss syndrome, 160 patients with severe preeclampsia, 80 patients with venous thromboembolism (VTE), 100 patients with placental abruption, 60 women with antenatal death. All patients and 500 healthy controls were tested to have genetic thrombophilia and antiphospholipid antibodies. Women with history of pregnancy complications received treatment in the preconception period and during pregnancy: low molecular weight heparin (LMWH) guided by D-dimer, aspirin, antioxidants, vitamins of B group, folic acid (up to 4 mg in women with hyperhomocysteinemia). Results: Thrombophilia was found in 75% of the women with fetal loss syndrome and antenatal death, in 96% of the women with recurrent preeclampsia, in 70% of the women with history of 1 episode of preeclampsia, in 80% of the women with placental abruption and in 100% of the women with VTE. In the study group nobody had moderate or severe forms of preeclampsia. Mild preeclampsia was observed in
S158 16%. All babies were alive. Preconception therapy allowed preventing recurrent fetal loss syndrome in 66%; 96% patients were delivered after 37 weeks. Patients had no recurrence of placental abruption or VTE. Conclusions: Thrombophilia might be the main pathogenetic mechanism of recurrent pregnancy complications. Due to thrombophilia involvement in trophoblast invasion and placentation, early treatment is essential. Preconception treatment with LMWH allows preventing recurrent pregnancy complications and fetal losses in most cases. P64 Thrombophilia as a universal mechanism of complications in clinical practice: presentation of a clinical case A.D. Makatsaria, V.O. Bitsadze. Department of Obstetrics and Gynecology, I.M. Sechenov Moscow Medical Academy, Russia Introduction: Throbmophilia represents multidiscinlinary problem that causes controversies in patients’ management. Material and Methods: We introduce a clinical case of management patient with thrombophilia. Results: Patient K, 45 years. History: 2005 y thrombectomy for concomitant embolic occlusion of left a. profundus femori and deep vein thrombosis 10 days after starting oral contraception. Screening for thrombophilia: Pt G20210A. FV Leiden, MTHFR C677T, PAI 4G/5G, fibrinogen 455 G/A heterozig. Platelet 85%, collagen 70%, ristomicine hyperaggregation: ADP 80%. Warfarin (INR 2 3) and clopidogrel were started. 2006 y hysterectomy due to metrorrhagia, submucous fibromyoma. Perioperative we used LMWH (guided by D-dimer) and then restarted warfarin (INR 2 3) + clopidogrel guided by aggregation tests. September 2008: pelvic pain, t 38ºC; ultrasound right ovarian cyst 10×8×9 cm with unhomogenous content. CA-125 near normal. Rightside ovariectomy was performed. Intraoperative diagnosis: apoplexy with festering. Perioperative LMWH was used. After 4 weeks: D-dimer 0.5 1 mcg/ml, moderate hyperaggregation (ADP 65%, collagen 55%, ristomidine 53%). Warfarin (INR 2 3) was restarted + aspirin 150 mg. Conclusions: Thrombophilia represents a serious problem that requires a multidisciplinary approach. Adequate balance between thrombothic and haemorragic complications may be sometimes difficult. Management patients with thrombophilia should include frequent control of thrombophilia markers including D-dimer, aggregation and INR if warfarin is used. Thrombophilia not only induces thrombosis but also aggravates haemorragic states due to predisposition to disseminated intravascular coagulation and inflammation. P65 A variety of clinical manifestations of antiphospholipid syndrome in obstetric practice J. Khizroeva. Department of Obstetrics and Gynecology, Moscow Sechenov Medical Academy, Moscow, Russia Background:: It is widely accepted that the presence of antiphospholipid antibodies (aPL) is associated with thrombosis. Antibodies to a variety of phospholipids now have been recognized and the consequences of these vascular occlusions are found in every organ and tissue. Objectives: We determined different obstetric, gynecological and endocrine manifestations in the APS and assessed whether these clinical situations are due to the presence of aPL. Methods:: During 2000 2008 we observed more than 700 patients with different obstetric and gynecological complications and APS (recurrent miscarriage, pre-eclampsia, placental thrombosis, fetal growth retardation, metabolic syndrome, infertility, venous and arterial thrombosis, hypopituitarism Sheehan’s syndrome, hormonal replacement therapy, oral contraceptives). Results:: The presence of autoantibodies to various phospholipids and phospholipids-binding proteins (antibodies) to
Abstracts selected for Poster Presentation b2-GPI, annexin V, prothrombin and to the antiphospholipid subtypes has been identified in 64% of the cases. In 71.5% APS was associated with genetic thrombophilia. Complex interactions of acquired and genetic thrombophilia are the worst combination and contribute to the causation of thrombotic events in most cases. We documented three cases of hypopituitarism after recurrent miscarriages in 2 cases and the third was in the postpartum period. All patients were aPL positive and two of them had high titers of antibodies to annexin V and prothrombin. Also we observed 110 newborns, whose mothers had APS. In 87 cases we found the circulations of aPL. Conclusions: The presence of aPL is an important thrombophilic risk factors and causes significant difficulties in obstetrics and gynecology. Laboratory testing for aPL has to be recommended routinely in the evaluation of patients with suspected thrombophilia. P66 Thrombophilia and systemic inflammation in pathogenesis of thrombotic complications of hormonal replacement therapy: potential of laboratory screening V.O. Bitsadze, S.V. Akinshina, A.D. Makatsaria. Department of Obstetrics and Gynecology, I.M. Sechenov Moscow Medical Academy, Russia Background: Hormonal replacement therapy (HRT) has been shown to be associated with arterial and venous thromboembolic complications. Nevertheless, pathogenic mechanisms of this phenomenon are not completely understood. Aims: To evaluate the role of multigenic thrombophilia and antiphospholipid syndrome (APS) as pathogenic factors of HRTinduced thrombosis. Methods: We examined 41 women with tromboembolic complications of oral HRT (deep vein thrombosis, pulmonary embolism, superficial thrombophlebitis, Budd-Chiary syndrome, retinal thrombosis, and stroke) for genetic thrombophilia and antiphospholipid antibodies (APA). Of note, 75.6% of the women had obstetric complications in their personal history (placental abruption, preeclampsia, fetal loss syndrome). Results: Thrombophilia was detected in 100% of the patients: APA in 43.9%; homozygous and heterozygous FV Leiden in 7.3% and 26.8% respectively; PAI-1 4G/5G polymorphism in 41.4%; prothrombin G20210A in 12.2%; homozygous and heterozygous GPIa 807C/T in 4.9% and 14.6 %, homozygous and heterozygous ACE I/D in 12.1 and 21.9% respectively; combination of genetic thrombophilia and APA-circulation in 36.6%; multigenic thrombophilia in 85.4%. Conclusions: Genetic thrombophilia and APS have synergic effect with HRT and may induce prothrombotic state due to the activation of coagulation, inflammation and endothelial dysfunction. Multigenic thrombophilia and combination of genetic and acquired (APS) thrombophilia might be the most unfavorable condition. Screening for thrombophilia seems to be useful before the administration of HRT. Special attention should be paid to the history of obstetrics complications. If thrombophilia was detected, HRT is absolutely contraindicated. P67 Diagnostic and prognostic role of proinflammatory cytokines polymorphisms in women with metabolic syndrome and history of sever preeclampsia Z.K. Gadaeva, S.M. Baimuradova, I. Abaeva, E. Breus. Department of obstetrics and gynecology, I.M. Sechenov Moscow Medical Academy, Russia Introduction: Recent evidence suggests the role of systemic inflammatory response syndrome (SIRS) in pathogenesis of preeclampsia (PE) and metabolic syndrome (MS).
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Conclusion: In most cases of abnormalities of the reproductive system the hemorrhagic changes in hemostasis combined form of AUB was observed. P62 Thrombophilia and prosthetic valve thrombosis in pregnancy S.V. Akinshina, V.O. Bitsadze, V.B. Nemirovskiy, N.T. Meskhi, A.D. Makatsaria. Department of Obstetrics and Gynecology, I.M. Sechenov Moscow Medical Academy, Russia Aim: To determine genetic thrombophilia and antiphospholipid antibodies (APA) in pregnant women with prosthetic valve thrombosis. Material and Methods: We have examined 8 pregnant women (25.7 ± 3.5 years) with mechanical valve thrombosis (mitral valve n = 6, aortic valve n = 1, tricuspid valve n = 1). Analysis of thrombophilia and APA was performed in all patients. Results: History of obstetric complications (recurrent fetal loss, intrauterine growth restriction, preeclampsia, antenatal death) was observed in 3 women. Thromboembolic complications were observed in 4 women (stroke n = 2, renal and spleen thrombosis n = 1, iliofemoral thrombosis after cesarean section n = 1). Before the admission to our hospital (in 8 28 weeks of gestation) 5 patients received warfarin without regular LMWH in low doses. 1 patient did monitoring, 3 patients not receive any anticoagulants in pregnancy during 1 month. Fetal mortality was 50% (n = 4). One patient died due to pulmonary embolism 48 hours after the simultaneous cesarean section and valve replacement. Multigenic thrombophilia (8805; 4 mutations concomitantly) and APA were detected in 100%. MTHFR C677T, PAI-1 675 4G/5G, t-PA I/D, F Hageman 46C/T, fibrinogen 455G/A, FV Leiden, prothrombin G20210A were detected in 6, 6, 2, 2, 4, 2 and 2 cases respectively. Lupus anticoagulant, anti-beta-glycoprotein I, anticardiolipins, antiannexin V antibodies were detected in 3, 6, 2 and 3 patients respectively. Conclusion: Prosthetic valve thrombosis in pregnancy may be associated with hypercoagulation state and inadequate anticoagulation in women with multigenic thrombophilia and APA-circulation. P63 Pregnancy management in women with history of obsteric complications: did thrombophilia change our strategy? A.D. Makatsaria, V.O. Bitsadze, S.M. Baimuradova, S.V. Akinshina. Department of Obstetrics and Gynecology, I.M. Sechenov Moscow Medical academy, Russia Aims: To determine genetic thrombophilia and to evaluate maternal and fetal outcomes in women with history of pregnancy complications receiving the preconception treatment. Material and methods: During the last 7 years we examined a total of 800 patients with history of pregnancy complications: 400 patients with fetal loss syndrome, 160 patients with severe preeclampsia, 80 patients with venous thromboembolism (VTE), 100 patients with placental abruption, 60 women with antenatal death. All patients and 500 healthy controls were tested to have genetic thrombophilia and antiphospholipid antibodies. Women with history of pregnancy complications received treatment in the preconception period and during pregnancy: low molecular weight heparin (LMWH) guided by D-dimer, aspirin, antioxidants, vitamins of B group, folic acid (up to 4 mg in women with hyperhomocysteinemia). Results: Thrombophilia was found in 75% of the women with fetal loss syndrome and antenatal death, in 96% of the women with recurrent preeclampsia, in 70% of the women with history of 1 episode of preeclampsia, in 80% of the women with placental abruption and in 100% of the women with VTE. In the study group nobody had moderate or severe forms of preeclampsia. Mild preeclampsia was observed in
S158 16%. All babies were alive. Preconception therapy allowed preventing recurrent fetal loss syndrome in 66%; 96% patients were delivered after 37 weeks. Patients had no recurrence of placental abruption or VTE. Conclusions: Thrombophilia might be the main pathogenetic mechanism of recurrent pregnancy complications. Due to thrombophilia involvement in trophoblast invasion and placentation, early treatment is essential. Preconception treatment with LMWH allows preventing recurrent pregnancy complications and fetal losses in most cases. P64 Thrombophilia as a universal mechanism of complications in clinical practice: presentation of a clinical case A.D. Makatsaria, V.O. Bitsadze. Department of Obstetrics and Gynecology, I.M. Sechenov Moscow Medical Academy, Russia Introduction: Throbmophilia represents multidiscinlinary problem that causes controversies in patients’ management. Material and Methods: We introduce a clinical case of management patient with thrombophilia. Results: Patient K, 45 years. History: 2005 y thrombectomy for concomitant embolic occlusion of left a. profundus femori and deep vein thrombosis 10 days after starting oral contraception. Screening for thrombophilia: Pt G20210A. FV Leiden, MTHFR C677T, PAI 4G/5G, fibrinogen 455 G/A heterozig. Platelet 85%, collagen 70%, ristomicine hyperaggregation: ADP 80%. Warfarin (INR 2 3) and clopidogrel were started. 2006 y hysterectomy due to metrorrhagia, submucous fibromyoma. Perioperative we used LMWH (guided by D-dimer) and then restarted warfarin (INR 2 3) + clopidogrel guided by aggregation tests. September 2008: pelvic pain, t 38ºC; ultrasound right ovarian cyst 10×8×9 cm with unhomogenous content. CA-125 near normal. Rightside ovariectomy was performed. Intraoperative diagnosis: apoplexy with festering. Perioperative LMWH was used. After 4 weeks: D-dimer 0.5 1 mcg/ml, moderate hyperaggregation (ADP 65%, collagen 55%, ristomidine 53%). Warfarin (INR 2 3) was restarted + aspirin 150 mg. Conclusions: Thrombophilia represents a serious problem that requires a multidisciplinary approach. Adequate balance between thrombothic and haemorragic complications may be sometimes difficult. Management patients with thrombophilia should include frequent control of thrombophilia markers including D-dimer, aggregation and INR if warfarin is used. Thrombophilia not only induces thrombosis but also aggravates haemorragic states due to predisposition to disseminated intravascular coagulation and inflammation. P65 A variety of clinical manifestations of antiphospholipid syndrome in obstetric practice J. Khizroeva. Department of Obstetrics and Gynecology, Moscow Sechenov Medical Academy, Moscow, Russia Background:: It is widely accepted that the presence of antiphospholipid antibodies (aPL) is associated with thrombosis. Antibodies to a variety of phospholipids now have been recognized and the consequences of these vascular occlusions are found in every organ and tissue. Objectives: We determined different obstetric, gynecological and endocrine manifestations in the APS and assessed whether these clinical situations are due to the presence of aPL. Methods:: During 2000 2008 we observed more than 700 patients with different obstetric and gynecological complications and APS (recurrent miscarriage, pre-eclampsia, placental thrombosis, fetal growth retardation, metabolic syndrome, infertility, venous and arterial thrombosis, hypopituitarism Sheehan’s syndrome, hormonal replacement therapy, oral contraceptives). Results:: The presence of autoantibodies to various phospholipids and phospholipids-binding proteins (antibodies) to
Abstracts selected for Poster Presentation b2-GPI, annexin V, prothrombin and to the antiphospholipid subtypes has been identified in 64% of the cases. In 71.5% APS was associated with genetic thrombophilia. Complex interactions of acquired and genetic thrombophilia are the worst combination and contribute to the causation of thrombotic events in most cases. We documented three cases of hypopituitarism after recurrent miscarriages in 2 cases and the third was in the postpartum period. All patients were aPL positive and two of them had high titers of antibodies to annexin V and prothrombin. Also we observed 110 newborns, whose mothers had APS. In 87 cases we found the circulations of aPL. Conclusions: The presence of aPL is an important thrombophilic risk factors and causes significant difficulties in obstetrics and gynecology. Laboratory testing for aPL has to be recommended routinely in the evaluation of patients with suspected thrombophilia. P66 Thrombophilia and systemic inflammation in pathogenesis of thrombotic complications of hormonal replacement therapy: potential of laboratory screening V.O. Bitsadze, S.V. Akinshina, A.D. Makatsaria. Department of Obstetrics and Gynecology, I.M. Sechenov Moscow Medical Academy, Russia Background: Hormonal replacement therapy (HRT) has been shown to be associated with arterial and venous thromboembolic complications. Nevertheless, pathogenic mechanisms of this phenomenon are not completely understood. Aims: To evaluate the role of multigenic thrombophilia and antiphospholipid syndrome (APS) as pathogenic factors of HRTinduced thrombosis. Methods: We examined 41 women with tromboembolic complications of oral HRT (deep vein thrombosis, pulmonary embolism, superficial thrombophlebitis, Budd-Chiary syndrome, retinal thrombosis, and stroke) for genetic thrombophilia and antiphospholipid antibodies (APA). Of note, 75.6% of the women had obstetric complications in their personal history (placental abruption, preeclampsia, fetal loss syndrome). Results: Thrombophilia was detected in 100% of the patients: APA in 43.9%; homozygous and heterozygous FV Leiden in 7.3% and 26.8% respectively; PAI-1 4G/5G polymorphism in 41.4%; prothrombin G20210A in 12.2%; homozygous and heterozygous GPIa 807C/T in 4.9% and 14.6 %, homozygous and heterozygous ACE I/D in 12.1 and 21.9% respectively; combination of genetic thrombophilia and APA-circulation in 36.6%; multigenic thrombophilia in 85.4%. Conclusions: Genetic thrombophilia and APS have synergic effect with HRT and may induce prothrombotic state due to the activation of coagulation, inflammation and endothelial dysfunction. Multigenic thrombophilia and combination of genetic and acquired (APS) thrombophilia might be the most unfavorable condition. Screening for thrombophilia seems to be useful before the administration of HRT. Special attention should be paid to the history of obstetrics complications. If thrombophilia was detected, HRT is absolutely contraindicated. P67 Diagnostic and prognostic role of proinflammatory cytokines polymorphisms in women with metabolic syndrome and history of sever preeclampsia Z.K. Gadaeva, S.M. Baimuradova, I. Abaeva, E. Breus. Department of obstetrics and gynecology, I.M. Sechenov Moscow Medical Academy, Russia Introduction: Recent evidence suggests the role of systemic inflammatory response syndrome (SIRS) in pathogenesis of preeclampsia (PE) and metabolic syndrome (MS).